Pub Date : 2025-09-01DOI: 10.1016/j.bpsc.2025.04.006
Jessica M. de Klerk-Sluis , Hanneke Geugies , Roel J.T. Mocking , Caroline A. Figueroa , Paul F.C. Groot , Jan-Bernard C. Marsman , Philip F.P. van Eijndhoven , Dirk E.M. Geurts , Henricus G. Ruhé
Background
Hypersensitivity to punishment is one of the core features of major depressive disorder (MDD). Hypersensitivity to punishment has been proposed to originate from aberrant aversive learning. One of the key areas in aversive learning is the habenula. Although evidence for dysfunctional aversive learning in patients with depression is well established, whether this dysfunction and its neural correlates persist during symptomatic remission of depression remains largely unexplored.
Methods
Functional magnetic resonance imaging data from 36 medication-free remitted patients with recurrent MDD and 27 healthy control participants participating in a Pavlovian classical conditioning task were assessed within a computational modeling framework to evaluate temporal difference–related activation of the habenula during aversive learning. Furthermore, generalized psychophysiological interaction analyses were performed to assess functional connectivity of the temporal difference signal with the habenula as an a priori region of interest.
Results
Relative to healthy control participants, patients showed significantly increased temporal difference–related aversive learning activation in the bilateral habenula. This activation was correlated with residual symptoms in the remitted MDD group. Furthermore, patients exhibited decreased functional connectivity between the habenula and the ventral tegmental area compared with control participants.
Conclusions
The increased habenula activity during aversive learning, particularly during the expectation of punishment, together with decreased functional habenula–ventral tegmental area connectivity in remitted patients with MDD, reflect hypersensitivity to and/or inability to regulate the impact of aversive environmental cues and punishment.
{"title":"Aberrant Aversive Learning Signals in the Habenula in Remitted Patients With Recurrent Depression","authors":"Jessica M. de Klerk-Sluis , Hanneke Geugies , Roel J.T. Mocking , Caroline A. Figueroa , Paul F.C. Groot , Jan-Bernard C. Marsman , Philip F.P. van Eijndhoven , Dirk E.M. Geurts , Henricus G. Ruhé","doi":"10.1016/j.bpsc.2025.04.006","DOIUrl":"10.1016/j.bpsc.2025.04.006","url":null,"abstract":"<div><h3>Background</h3><div>Hypersensitivity to punishment is one of the core features of major depressive disorder (MDD). Hypersensitivity to punishment has been proposed to originate from aberrant aversive learning. One of the key areas in aversive learning is the habenula. Although evidence for dysfunctional aversive learning in patients with depression is well established, whether this dysfunction and its neural correlates persist during symptomatic remission of depression remains largely unexplored.</div></div><div><h3>Methods</h3><div>Functional magnetic resonance imaging data from 36 medication-free remitted patients with recurrent MDD and 27 healthy control participants participating in a Pavlovian classical conditioning task were assessed within a computational modeling framework to evaluate temporal difference–related activation of the habenula during aversive learning. Furthermore, generalized psychophysiological interaction analyses were performed to assess functional connectivity of the temporal difference signal with the habenula as an a priori region of interest.</div></div><div><h3>Results</h3><div>Relative to healthy control participants, patients showed significantly increased temporal difference–related aversive learning activation in the bilateral habenula. This activation was correlated with residual symptoms in the remitted MDD group. Furthermore, patients exhibited decreased functional connectivity between the habenula and the ventral tegmental area compared with control participants.</div></div><div><h3>Conclusions</h3><div>The increased habenula activity during aversive learning, particularly during the expectation of punishment, together with decreased functional habenula–ventral tegmental area connectivity in remitted patients with MDD, reflect hypersensitivity to and/or inability to regulate the impact of aversive environmental cues and punishment.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 9","pages":"Pages 978-987"},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-01DOI: 10.1016/j.bpsc.2025.06.004
Jason Smucny
{"title":"Machine Learning–Based Clinical Prediction Models in Psychopathology: Can Transfer Learning Fix the “Illusory Generalizability” Problem?","authors":"Jason Smucny","doi":"10.1016/j.bpsc.2025.06.004","DOIUrl":"10.1016/j.bpsc.2025.06.004","url":null,"abstract":"","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 9","pages":"Pages 897-899"},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01DOI: 10.1016/j.bpsc.2024.09.001
Ju-Chi Yu , Colin Hawco , Lucy Bassman , Lindsay D. Oliver , Miklos Argyelan , James M. Gold , Sunny X. Tang , George Foussias , Robert W. Buchanan , Anil K. Malhotra , Stephanie H. Ameis , Aristotle N. Voineskos , Erin W. Dickie
Background
Schizophrenia spectrum disorders (SSDs), which are characterized by social cognitive deficits, have been associated with dysconnectivity in unimodal (e.g., visual, auditory) and multimodal (e.g., default mode and frontoparietal) cortical networks. However, little is known about how such dysconnectivity is related to social and nonsocial cognition and how such brain-behavior relationships associate with clinical outcomes of SSDs.
Methods
We analyzed cognitive (nonsocial and social) measures and resting-state functional magnetic resonance imaging data from the SPINS [Social Processes Initiative in Neurobiology of the Schizophrenia(s)] study (247 stable participants with SSDs and 172 healthy control participants, ages 18–55 years). We extracted gradients from parcellated connectomes and examined the association between the first 3 gradients and the cognitive measures using partial least squares correlation (PLSC). We then correlated the PLSC dimensions with functioning and symptoms in the SSD group.
Results
The SSD group showed significantly lower differentiation on all 3 gradients. The first PLSC dimension explained 68.53% (p < .001) of the covariance and showed a significant difference between the SSD and the control group (bootstrap p < .05). PLSC showed that all cognitive measures were associated with gradient scores of unimodal and multimodal networks (gradient 1); auditory, sensorimotor, and visual networks (gradient 2); and perceptual networks and the striatum (gradient 3), which were less differentiated in SSDs. Furthermore, the first dimension was positively correlated with negative symptoms and functioning in the SSD group.
Conclusions
These results suggest a potential role of lower differentiation of brain networks in cognitive and functional impairments in SSDs.
{"title":"Multivariate Association Between Functional Connectivity Gradients and Cognition in Schizophrenia Spectrum Disorders","authors":"Ju-Chi Yu , Colin Hawco , Lucy Bassman , Lindsay D. Oliver , Miklos Argyelan , James M. Gold , Sunny X. Tang , George Foussias , Robert W. Buchanan , Anil K. Malhotra , Stephanie H. Ameis , Aristotle N. Voineskos , Erin W. Dickie","doi":"10.1016/j.bpsc.2024.09.001","DOIUrl":"10.1016/j.bpsc.2024.09.001","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia spectrum disorders (SSDs), which are characterized by social cognitive deficits, have been associated with dysconnectivity in unimodal (e.g., visual, auditory) and multimodal (e.g., default mode and frontoparietal) cortical networks. However, little is known about how such dysconnectivity is related to social and nonsocial cognition and how such brain-behavior relationships associate with clinical outcomes of SSDs.</div></div><div><h3>Methods</h3><div>We analyzed cognitive (nonsocial and social) measures and resting-state functional magnetic resonance imaging data from the SPINS [Social Processes Initiative in Neurobiology of the Schizophrenia(s)] study (247 stable participants with SSDs and 172 healthy control participants, ages 18–55 years). We extracted gradients from parcellated connectomes and examined the association between the first 3 gradients and the cognitive measures using partial least squares correlation (PLSC). We then correlated the PLSC dimensions with functioning and symptoms in the SSD group.</div></div><div><h3>Results</h3><div>The SSD group showed significantly lower differentiation on all 3 gradients. The first PLSC dimension explained 68.53% (<em>p</em> < .001) of the covariance and showed a significant difference between the SSD and the control group (bootstrap <em>p</em> < .05). PLSC showed that all cognitive measures were associated with gradient scores of unimodal and multimodal networks (gradient 1); auditory, sensorimotor, and visual networks (gradient 2); and perceptual networks and the striatum (gradient 3), which were less differentiated in SSDs. Furthermore, the first dimension was positively correlated with negative symptoms and functioning in the SSD group.</div></div><div><h3>Conclusions</h3><div>These results suggest a potential role of lower differentiation of brain networks in cognitive and functional impairments in SSDs.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 8","pages":"Pages 833-845"},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01DOI: 10.1016/j.bpsc.2024.12.015
Guosong Shang , Tao Zhou , Xinyuan Yan , Kunyu He , Bin Liu , Zhebin Feng , Junpeng Xu , Xinguang Yu , Yanyang Zhang
Background
Chronic cortisol overexposure plays a significant role in the development of neuropathological changes associated with neuropsychiatric and neurodegenerative disorders. The hippocampus, the primary target of cortisol, may exhibit characteristic regional responses due to its internal heterogeneity. In this study, we explored structural and functional alterations of hippocampal (HP) subfields in Cushing’s disease (CD), an endogenous model of chronic cortisol overexposure.
Methods
Utilizing structural and resting-state functional magnetic resonance imaging data from 169 participants (86 patients with CD and 83 healthy control participants [HCs]) recruited from a single center, we investigated specific structural changes in HP subfields and explored the functional connectivity alterations driven by these structural abnormalities. We also analyzed potential associative mechanisms between these changes and biological attributes, neuropsychiatric representations, cognitive function, and gene expression profiles.
Results
Compared with HCs, patients with CD exhibited significant bilateral volume reductions in multiple HP subfields. Notably, volumetric decreases in the left HP body and tail subfields were significantly correlated with cortisol levels, Montreal Cognitive Assessment scores, and quality of life measures. Disrupted connectivity between the structurally abnormal HP subfields and the ventromedial prefrontal cortex may impair reward-based decision making and emotional regulation, with this dysconnectivity being linked to structural changes in right HP subfields. Another region that exhibited dysconnectivity was located in the left pallidum and putamen. Gene expression patterns associated with synaptic components may underlie these macrostructural alterations.
Conclusions
Our findings elucidate the subfield-specific effects of chronic cortisol overexposure on the hippocampus, enhancing understanding of shared neuropathological traits linked to cortisol dysregulation in neuropsychiatric and neurodegenerative disorders.
{"title":"Multiscale Analysis Reveals Hippocampal Subfield Vulnerabilities to Chronic Cortisol Overexposure: Evidence From Cushing’s Disease","authors":"Guosong Shang , Tao Zhou , Xinyuan Yan , Kunyu He , Bin Liu , Zhebin Feng , Junpeng Xu , Xinguang Yu , Yanyang Zhang","doi":"10.1016/j.bpsc.2024.12.015","DOIUrl":"10.1016/j.bpsc.2024.12.015","url":null,"abstract":"<div><h3>Background</h3><div>Chronic cortisol overexposure plays a significant role in the development of neuropathological changes associated with neuropsychiatric and neurodegenerative disorders. The hippocampus, the primary target of cortisol, may exhibit characteristic regional responses due to its internal heterogeneity. In this study, we explored structural and functional alterations of hippocampal (HP) subfields in Cushing’s disease (CD), an endogenous model of chronic cortisol overexposure.</div></div><div><h3>Methods</h3><div>Utilizing structural and resting-state functional magnetic resonance imaging data from 169 participants (86 patients with CD and 83 healthy control participants [HCs]) recruited from a single center, we investigated specific structural changes in HP subfields and explored the functional connectivity alterations driven by these structural abnormalities. We also analyzed potential associative mechanisms between these changes and biological attributes, neuropsychiatric representations, cognitive function, and gene expression profiles.</div></div><div><h3>Results</h3><div>Compared with HCs, patients with CD exhibited significant bilateral volume reductions in multiple HP subfields. Notably, volumetric decreases in the left HP body and tail subfields were significantly correlated with cortisol levels, Montreal Cognitive Assessment scores, and quality of life measures. Disrupted connectivity between the structurally abnormal HP subfields and the ventromedial prefrontal cortex may impair reward-based decision making and emotional regulation, with this dysconnectivity being linked to structural changes in right HP subfields. Another region that exhibited dysconnectivity was located in the left pallidum and putamen. Gene expression patterns associated with synaptic components may underlie these macrostructural alterations.</div></div><div><h3>Conclusions</h3><div>Our findings elucidate the subfield-specific effects of chronic cortisol overexposure on the hippocampus, enhancing understanding of shared neuropathological traits linked to cortisol dysregulation in neuropsychiatric and neurodegenerative disorders.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 8","pages":"Pages 865-876"},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01DOI: 10.1016/j.bpsc.2025.02.007
Ekaterina Shatalina , Thomas Whitehurst , Ellis Chika Onwordi , Alexander Whittington , Ayla Mansur , Atheeshaan Arumuham , Tiago Reis Marques , Roger N. Gunn , Sridhar Natesan , Matthew M. Nour , Eugenii A. Rabiner , Matthew B. Wall , Oliver D. Howes
Background
Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be noninvasively measured using [18F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level–dependent (BOLD) response and impairments in cognition. In this study, we aimed to investigate the relationship between mitochondrial complex I levels, cognitive function, and associated neural activity during task switching in healthy humans.
Methods
Cognitively healthy adults (N = 23) underwent [18F]BCPP-EF PET scans and functional magnetic resonance imaging (fMRI) while performing a task-switching exercise. Task performance metrics included switch cost and switching accuracy. Data were analyzed using linear mixed-effects models and partial least squares regression (PLS-R).
Results
We found significant positive associations between [18F]BCPP-EF volume of distribution (VT) and the task-switching fMRI response (β = 3.351, SE = 1.01, z = 3.249, p = .001). Positive Pearson’s correlations between [18F]BCPP-EF VT and the fMRI response were observed in the dorsolateral prefrontal cortex (r = 0.61, p = .0019), insula (r = 0.46, p = .0264), parietal precuneus (r = 0.51, p = .0139), and anterior cingulate cortex (r = 0.45, p = .0293). [18F]BCPP-EF VT across task-relevant regions was associated with task switching accuracy (PLS-R, R2 = 0.48, root mean square error [RMSE] = 0.154, p = .011) and with switch cost (PLS-R, R2 = 0.38, RMSE = 0.07, p = .048).
Conclusions
Higher mitochondrial complex I levels may underlie an individual’s ability to exhibit a stronger BOLD response during task switching and are associated with better task-switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for the aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction that should be tested in future studies.
{"title":"Mitochondria and Cognition: An [18F]BCPP-EF Positron Emission Tomography Study of Mitochondrial Complex I Levels and Brain Activation During Task Switching","authors":"Ekaterina Shatalina , Thomas Whitehurst , Ellis Chika Onwordi , Alexander Whittington , Ayla Mansur , Atheeshaan Arumuham , Tiago Reis Marques , Roger N. Gunn , Sridhar Natesan , Matthew M. Nour , Eugenii A. Rabiner , Matthew B. Wall , Oliver D. Howes","doi":"10.1016/j.bpsc.2025.02.007","DOIUrl":"10.1016/j.bpsc.2025.02.007","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial complex I is the largest enzyme complex in the respiratory chain and can be noninvasively measured using [<sup>18</sup>F]BCPP-EF positron emission tomography (PET). Neurological conditions associated with mitochondria complex I pathology are also associated with altered blood oxygen level–dependent (BOLD) response and impairments in cognition. In this study, we aimed to investigate the relationship between mitochondrial complex I levels, cognitive function, and associated neural activity during task switching in healthy humans.</div></div><div><h3>Methods</h3><div>Cognitively healthy adults (<em>N</em> = 23) underwent [<sup>18</sup>F]BCPP-EF PET scans and functional magnetic resonance imaging (fMRI) while performing a task-switching exercise. Task performance metrics included switch cost and switching accuracy. Data were analyzed using linear mixed-effects models and partial least squares regression (PLS-R).</div></div><div><h3>Results</h3><div>We found significant positive associations between [<sup>18</sup>F]BCPP-EF volume of distribution (V<sub>T</sub>) and the task-switching fMRI response (β = 3.351, SE = 1.01, <em>z</em> = 3.249, <em>p</em> = .001). Positive Pearson’s correlations between [<sup>18</sup>F]BCPP-EF V<sub>T</sub> and the fMRI response were observed in the dorsolateral prefrontal cortex (<em>r</em> = 0.61, <em>p</em> = .0019), insula (<em>r</em> = 0.46, <em>p</em> = .0264), parietal precuneus (<em>r</em> = 0.51, <em>p</em> = .0139), and anterior cingulate cortex (<em>r</em> = 0.45, <em>p</em> = .0293). [<sup>18</sup>F]BCPP-EF V<sub>T</sub> across task-relevant regions was associated with task switching accuracy (PLS-R, <em>R</em><sup>2</sup> = 0.48, root mean square error [RMSE] = 0.154, <em>p</em> = .011) and with switch cost (PLS-R, <em>R</em><sup>2</sup> = 0.38, RMSE = 0.07, <em>p</em> = .048).</div></div><div><h3>Conclusions</h3><div>Higher mitochondrial complex I levels may underlie an individual’s ability to exhibit a stronger BOLD response during task switching and are associated with better task-switching performance. This provides the first evidence linking the BOLD response with mitochondrial complex I and suggests a possible biological mechanism for the aberrant BOLD response in conditions associated with mitochondrial complex I dysfunction that should be tested in future studies.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 8","pages":"Pages 823-832"},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01DOI: 10.1016/j.bpsc.2025.03.009
Wanrong Peng , Suyao Liu , Jinyao Yi
Background
Major depressive disorder (MDD) and borderline personality disorder (BPD) involve substantial impairments in negative and positive emotion processing. This meta-analysis aims to identify both transdiagnostic and disorder-specific neural abnormalities during the processing of negative and positive stimuli for MDD and BPD.
Methods
The current coordinate-based and image-based meta-analyses comprised 42 functional magnetic resonance imaging studies involving MDD (42 negative studies vs. 22 positive studies; 1532 patients with MDD vs. 1481 healthy controls) and 25 involving BPD (23 negative studies vs. 7 positive studies; 522 patients with BPD vs. 519 healthy controls).
Results
Compared with healthy controls, patients with MDD exhibited hyporeactivity in the left precentral gyrus during negative emotion processing and decreased activation in left temporal lobe, insula, and bilateral anterior cingulate cortex during positive emotion processing, while patients with BPD displayed hyperreactivity in the left hippocampus and amygdala and hyporeactivity in the right inferior frontal gyrus during negative emotion processing. Compared with BPD, patients with MDD exhibited greater hyporeactivity in the bilateral anterior cingulate cortex during negative emotion processing and in the left middle temporal gyrus during positive emotion processing. The transdiagnostic hyporeactivity of BPD and MDD was mainly located in the left inferior and right middle frontal gyrus during negative emotion processing.
Conclusions
Our findings highlight both distinct and transdiagnostic neural mechanisms of emotion processing in MDD and BPD.
{"title":"Transdiagnostic and Disorder-Specific Neural Correlates of Emotion Processing in Major Depressive Disorder and Borderline Personality Disorder: Coordinate-Based and Image-Based Comparative Meta-Analyses","authors":"Wanrong Peng , Suyao Liu , Jinyao Yi","doi":"10.1016/j.bpsc.2025.03.009","DOIUrl":"10.1016/j.bpsc.2025.03.009","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) and borderline personality disorder (BPD) involve substantial impairments in negative and positive emotion processing. This meta-analysis aims to identify both transdiagnostic and disorder-specific neural abnormalities during the processing of negative and positive stimuli for MDD and BPD.</div></div><div><h3>Methods</h3><div>The current coordinate-based and image-based meta-analyses comprised 42 functional magnetic resonance imaging studies involving MDD (42 negative studies vs. 22 positive studies; 1532 patients with MDD vs. 1481 healthy controls) and 25 involving BPD (23 negative studies vs. 7 positive studies; 522 patients with BPD vs. 519 healthy controls).</div></div><div><h3>Results</h3><div>Compared with healthy controls, patients with MDD exhibited hyporeactivity in the left precentral gyrus during negative emotion processing and decreased activation in left temporal lobe, insula, and bilateral anterior cingulate cortex during positive emotion processing, while patients with BPD displayed hyperreactivity in the left hippocampus and amygdala and hyporeactivity in the right inferior frontal gyrus during negative emotion processing. Compared with BPD, patients with MDD exhibited greater hyporeactivity in the bilateral anterior cingulate cortex during negative emotion processing and in the left middle temporal gyrus during positive emotion processing. The transdiagnostic hyporeactivity of BPD and MDD was mainly located in the left inferior and right middle frontal gyrus during negative emotion processing.</div></div><div><h3>Conclusions</h3><div>Our findings highlight both distinct and transdiagnostic neural mechanisms of emotion processing in MDD and BPD.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 8","pages":"Pages 883-894"},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-01DOI: 10.1016/j.bpsc.2025.01.002
Kevin Handoko , Alyssa Neppach , Ian Snyder , Helmet T. Karim , Alexandre Y. Dombrovski , Marta Peciña
Background
Acute experimental models of antidepressant placebo effects suggest that expectancies, encoded within the salience network (SN), are reinforced by sensory evidence and mood fluctuations. However, whether these dynamics extend to longer timescales remains unknown. To answer this question, we investigated how SN and default mode network (DMN) functional connectivity during the processing of antidepressant expectancies facilitates the shift from salience attribution to contextual cues in the SN to belief-induced mood responses in the DMN, both acutely and long term.
Methods
Sixty psychotropic-free patients with major depressive disorder completed an acute antidepressant placebo functional magnetic resonance imaging experiment manipulating placebo-associated expectancies and their reinforcement while assessing trial-by-trial mood improvement before entering an 8-week double-blind, randomized, placebo-controlled trial of a selective serotonin reuptake inhibitor or placebo.
Results
Learned antidepressant expectancies predicted by a reinforcement learning model modulated SN-DMN connectivity. Acutely, greater modulation predicted higher effects of expectancy and reinforcement manipulations on reported expectancies and mood. Over 8 weeks, no significant drug effects on mood improvement were observed. However, participants who believed that they were receiving an antidepressant exhibited significantly greater mood improvement irrespective of the actual treatment received. Moreover, increased SN-DMN connectivity predicted mood improvement, especially in placebo-treated participants who believed that they received a selective serotonin reuptake inhibitor.
Conclusions
SN-DMN interactions may play a critical role in the evolution of antidepressant response expectancies, drug-assignment beliefs, and their effects on mood.
{"title":"Expectancy-Mood Neural Dynamics Predict Mechanisms of Short- and Long-Term Antidepressant Placebo Effects","authors":"Kevin Handoko , Alyssa Neppach , Ian Snyder , Helmet T. Karim , Alexandre Y. Dombrovski , Marta Peciña","doi":"10.1016/j.bpsc.2025.01.002","DOIUrl":"10.1016/j.bpsc.2025.01.002","url":null,"abstract":"<div><h3>Background</h3><div>Acute experimental models of antidepressant placebo effects suggest that expectancies, encoded within the salience network (SN), are reinforced by sensory evidence and mood fluctuations. However, whether these dynamics extend to longer timescales remains unknown. To answer this question, we investigated how SN and default mode network (DMN) functional connectivity during the processing of antidepressant expectancies facilitates the shift from salience attribution to contextual cues in the SN to belief-induced mood responses in the DMN, both acutely and long term.</div></div><div><h3>Methods</h3><div>Sixty psychotropic-free patients with major depressive disorder completed an acute antidepressant placebo functional magnetic resonance imaging experiment manipulating placebo-associated expectancies and their reinforcement while assessing trial-by-trial mood improvement before entering an 8-week double-blind, randomized, placebo-controlled trial of a selective serotonin reuptake inhibitor or placebo.</div></div><div><h3>Results</h3><div>Learned antidepressant expectancies predicted by a reinforcement learning model modulated SN-DMN connectivity. Acutely, greater modulation predicted higher effects of expectancy and reinforcement manipulations on reported expectancies and mood. Over 8 weeks, no significant drug effects on mood improvement were observed. However, participants who believed that they were receiving an antidepressant exhibited significantly greater mood improvement irrespective of the actual treatment received. Moreover, increased SN-DMN connectivity predicted mood improvement, especially in placebo-treated participants who believed that they received a selective serotonin reuptake inhibitor.</div></div><div><h3>Conclusions</h3><div>SN-DMN interactions may play a critical role in the evolution of antidepressant response expectancies, drug-assignment beliefs, and their effects on mood.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 8","pages":"Pages 794-803"},"PeriodicalIF":4.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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